This invention relates to implantable encapsulation devices for the treatment of diseases and disorders with encapsulated cells or substances such as neurotransmitters, neuromodulators, hormones, trophic factors, growth factors, analgesics, enzymes, antibodies or other biologically active molecules. In particular, the invention relates to internally-supported, biocompatible cell encapsulation devices.
One encapsulation approach has been macroencapsulation, which typically involves loading living cells into hollow fiber (or other suitable shape) devices and then sealing the extremities. The encapsulation of such cells by a selectively permeable, or "permselective", membrane permits diffusion of the biological factors produced and secreted by the cells yet restrains the cells within a specific location. Encapsulation may also reduce or prevent host rejection in the case of xenogeneic (cross-species) or allogeneic transplantation.
Various types of cell devices are known. U.S. Pat. No. 4,892,538, to Aebischer et al. (incorporated herein by reference), discloses a selectively permeable hollow fiber membrane for cell encapsulation. U.S. Pat. No. 5,158,881, also to Aebischer et al. (incorporated herein by reference), discloses a method for encapsulating viable cells by forming a tubular extrudate around a cell suspension and sealing the tubular extrudate at intervals to define separate cell compartments joined by polymeric links. See also Mandel et al. (WO 91/00119), which refers to a selectively permeable cell closeable membrane tube for implantation in a subject having a large pore hydrophobic outer surface to encourage vascularization.
Many cell types used in encapsulated devices are of the adherent type, and (whether dividing or non-dividing) will aggregate and adhere to one another. These cell clusters or aggregations may form a necrotic core in the center of the device. Such a core may develop over time due to a shortage of certain metabolites reaching the center of the cell cluster or to the buildup of toxic products, causing cells to die. As dying cells accumulate and begin to break down, the necrotic tissue may also release factors which are detrimental to the surviving cells (e.g., factors which elicit a macrophage or other immune response).
One approach to reducing formation of a necrotic core involves immobilizing cells in a matrix material, e,g, a hydrogel matrix, within the device. See, e.g., Dionne et al. (WO 92/19195) which refers to biocompatible immunoisolatory vehicles with a hydrogel or extracellular matrix core.
Another known approach to controlling growth of cells in the device and to reducing necrotic core effects is to provide poly(hydroxyethyl methacylate) or poly(hydroxyethyl methacrylate-co-methyl methacrylate) or non-woven polyester scaffold for cells to grow on inside the device. See, e.g., Schinstine et al. (WO 96/02646). Such scaffolds form a fibrous net, not an open cell structure.